Abstract CT541: Efficacy and safety of parsaclisib-ruxolitinib combination therapy in myelofibrosis patients (Pts) with low vs higher baseline platelet count (PC): A subgroup analysis of data from a phase 2 study
Authors: Abdulraheem Yacoub, Uma Borate, Raajit Rampal, Haris Ali, Eunice Wang, Aaron Gerds, Gabriela Hobbs, Marina Kremyanskaya, Elliott Winton, Casey O’Connell, Swati Goel, Stephen Oh, Gary Schiller, Albert Assad, Sue Erickson-Viitanen, Feng Zhou, Naval Daver
Journal: Cancer Research (2022)

Abstract Background: Myelofibrosis (MF) pts often exhibit suboptimal response to chronic ruxolitinib therapy, possibly due to persistent PI3K pathway activation. In the ongoing phase 2 INCB 50465-201 trial (NCT02718300), add on parsaclisib (potent, highly selective PI3Kδ inhibitor) is showing preliminary efficacy in MF pts with suboptimal ruxolitinib response. JAK inhibitors (eg, ruxolitinib), are associated with thrombocytopenia; therefore, pts with low PC are commonly more difficult to treat. We present a subgroup analysis of efficacy and safety data from INCB 50465-201 by baseline PC. Methods: Eligible adults had primary/secondary MF with suboptimal response (palpable spleen &amp;gt;10 cm below left subcostal margin [LSM]; or palpable spleen 5-10 cm below LSM and active symptoms) after ≥6 months of ruxolitinib monotherapy (5-25 mg BID; stable dose ≥8 wks). Pts remained on their last stable ruxolitinib dose and received add on parsaclisib (10 or 20 mg QD for 8 wks; same dose QW thereafter) or parsaclisib (5 or 20 mg QD for 8 wks; 5 mg QD thereafter). For this analysis, spleen volume (SV), total symptom score (TSS) assessed by Myelofibrosis-Symptoms Assessment Form (MFSAF) v3.0 daily diary, and safety, were evaluated by baseline PC (low PC, 50-&amp;lt;100 × 109/L; higher PC, ≥100 × 109/L). Results: At data cutoff (8/27/2020), 67 pts were enrolled (low PC, n=21; higher PC, n=46; median age 68 y). For low vs higher PC, median prior duration of ruxolitinib use was 34.7 vs 14.9 months; baseline symptoms were worse for low PC vs higher PC (median [range] MFSAF-TSS, 21.4 [0.6-47] vs 10 [0-43]). For low vs higher PC, 9/18 (50.0%) vs 15/38 (39.4%) pts had SV reduction (SVR) ≥10% at wk 12; percentages of pts with SVR ≥10% were similar at wk 24 (6/17 [35.2%] vs 13/35 [37.1%]); 0 vs 1 pt had SVR ≥35% at wk 12; 2 vs 1 pt had SVR ≥35% at wk 24. Of pts with ≥10% SVR at wk 24, 4/6 with low PC and 9/13 with higher PC were on all daily dosing regimens. For low vs higher PC, median (range) percentage change in MFSAF-TSS was −20.5 (−56.6 to +17.1) vs −22.2 (−100 to +500) at wk 12; −26.1 (−54.7 to +2.4) vs −23.1 (−91.3 to +222.5) at wk 24. In both subgroups, nonhematologic treatment-emergent adverse events (TEAEs) were mostly grade 1/2. Most common (≥20%) TEAEs were dyspnea (33%), falls (33%), peripheral edema (29%), and nasal congestion (24%) for low PC; diarrhea (28%), nausea (24%), abdominal pain (24%), cough (20%), and fatigue (20%) for higher PC. For low vs higher PC, 9/21 (43%) vs 3/46 (7%) pts had parsaclisib dose interruption due to thrombocytopenia; 1 pt with low PC had ruxolitinib interruption due to thrombocytopenia. Conclusion: Add-on parsaclisib showed efficacy in pts from both low and higher baseline PC groups. Given the acceptable safety profile and efficacy of add-on parsaclasib, MF pts with both low and higher PC may be able to benefit from parsaclisib-ruxolitinib combination therapy. Citation Format: Abdulraheem Yacoub, Uma Borate, Raajit Rampal, Haris Ali, Eunice Wang, Aaron Gerds, Gabriela Hobbs, Marina Kremyanskaya, Elliott Winton, Casey O’Connell, Swati Goel, Stephen Oh, Gary Schiller, Albert Assad, Sue Erickson-Viitanen, Feng Zhou, Naval Daver. Efficacy and safety of parsaclisib-ruxolitinib combination therapy in myelofibrosis patients (Pts) with low vs higher baseline platelet count (PC): A subgroup analysis of data from a phase 2 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT541.